37 research outputs found

    Oxygen conserving mitochondrial adaptations in the skeletal muscles of breath hold divers

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    BackgroundThe performance of elite breath hold divers (BHD) includes static breath hold for more than 11 minutes, swimming as far as 300 m, or going below 250 m in depth, all on a single breath of air. Diving mammals are adapted to sustain oxidative metabolism in hypoxic conditions through several metabolic adaptations, including improved capacity for oxygen transport and mitochondrial oxidative phosphorylation in skeletal muscle. It was hypothesized that similar adaptations characterized human BHD. Hence, the purpose of this study was to examine the capacity for oxidative metabolism in skeletal muscle of BHD compared to matched controls.MethodsBiopsies were obtained from the lateral vastus of the femoral muscle from 8 Danish BHD and 8 non-diving controls (Judo athletes) matched for morphometry and whole body VO2max. High resolution respirometry was used to determine mitochondrial respiratory capacity and leak respiration with simultaneous measurement of mitochondrial H2O2 emission. Maximal citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogenase (HAD) activity were measured in muscle tissue homogenates. Western Blotting was used to determine protein contents of respiratory complex I-V subunits and myoglobin in muscle tissue lysates.ResultsMuscle biopsies of BHD revealed lower mitochondrial leak respiration and electron transfer system (ETS) capacity and higher H2O2 emission during leak respiration than controls, with no differences in enzyme activities (CS and HAD) or protein content of mitochondrial complex subunits myoglobin, myosin heavy chain isoforms, markers of glucose metabolism and antioxidant enzymes.ConclusionWe demonstrated for the first time in humans, that the skeletal muscles of BHD are characterized by lower mitochondrial oxygen consumption both during low leak and high (ETS) respiration than matched controls. This supports previous observations of diving mammals demonstrating a lower aerobic mitochondrial capacity of the skeletal muscles as an oxygen conserving adaptation during prolonged dives.</div

    Vce as early indicator of IGBT module failure mode

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    Hepatic sinusoidal obstruction syndrome and short-term application of 6-thioguanine in pediatric acute lymphoblastic leukemia

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    Long-term treatment with 6-thioguanine (6-TG) for pediatric acute lymphoblastic leukemia (ALL) is associated with high rates of hepatic sinusoidal obstruction syndrome (SOS). Nevertheless, current treatment continues to use short-term applications of 6-TG with only sparse information on toxicity. 6-TG is metabolized by thiopurine methyltransferase (TPMT) which underlies clinically relevant genetic polymorphism. We analyzed the association between hepatic SOS reported as a serious adverse event (SAE) and short-term 6-TG application in 3983 pediatric ALL patients treated on trial AIEOP-BFM ALL 2000 (derivation cohort) and defined the role of TPMT genotype in this relationship. We identified 17 patients (0.43%) with hepatic SOS, 13 of which with short-term exposure to 6-TG (P < 0.0001). Eight of the 13 patients were heterozygous for low-activity TPMT variants, resulting in a 22.4-fold (95% confidence interval 7.1–70.7; P ≤ 0.0001) increased risk of hepatic SOS for heterozygotes in comparison to TPMT wild-type patients. Results were supported by independent replication analysis. All patients with hepatic SOS after short-term 6-TG recovered and did not demonstrate residual symptoms. Thus, hepatic SOS is associated with short-term exposure to 6-TG during treatment of pediatric ALL and SOS risk is increased for patients with low-activity TPMT genotypes

    From the social to the systematic

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    Large design and manufacturing projects are conducted in elaborate settings. Interdependent specialists work together, building complex systems. A substantial part of their daily work concerns the coordination of distributed work. This paper reports from a field study at Foss Electric, a Danish manufacturing company, where the development of an instrument for testing the quality of raw milk was studied. Scheduled and informal project meetings together with paper-based coordination systems were the primary means of managing the complexity of coordinating work within the project. This paper investigates the origination, use, and function of these coordination mechanisms applying a Coordination Mechanism perspective (Schmidt and Simone, 1996). We argue that the complexity of coordinating distributed work in large design projects result in the adoption of coordination systems. These systems formalize aspects of coordination work through artifacts, procedures for use and conventions

    Measurement of the Th 229 Isomer Energy with a Magnetic Microcalorimeter

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    We present a measurement of the low-energy (0--60\,keV) γ\gamma ray spectrum produced in the α\alpha-decay of 233^{233}U using a dedicated cryogenic magnetic micro-calorimeter. The energy resolution of \sim1010\,eV, together with exceptional gain linearity, allow us to measure the energy of the low-lying isomeric state in 229^{229}Th using four complementary evaluation schemes. The most accurate scheme determines the 229^{229}Th isomer energy to be 8.10(17)8.10(17)\,eV, corresponding to 153.1(37)\,nm, superseding in precision previous values based on γ\gamma spectroscopy, and agreeing with a recent measurement based on internal conversion electrons. We also measure branching ratios of the relevant excited states to be b29=9.3(6)%b_{29}=9.3(6)\% and b42=0.3(3)%b_{42}=0.3(3)\%.Comment: 5 pages, 5 figures + supplementar
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